MET Amplification and Efficacy of Nivolumab in Patients With NSCLC

Yoshimura, Katsuhiro; Inoue, Yusuke; Inui, Naoki; Karayama, Masato; Yasui, Hideki; Hozumi, Hironao; Suzuki, Yuzo; Furuhashi, Kazuki; Fujisawa, Tomoyuki; Enomoto, Noriyuki; Nakamura, Yutaro; Sugimura, Haruhiko; Suda, Takafumi

doi:10.1016/j.jtocrr.2021.100239

Cited by 6 publications

(10 citation statements)

References 51 publications

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“… 24 A subgroup analysis of the PROFILE 1001 study showed that the ORR in the high MET amplification group (MET/CEP7 ≥ 4.0) was 38.1% with a median PFS of 6.7 months, which was significantly higher than that of the medium or low MET amplification group. 25 In our study, the correlation between MET amplification GCN and prognosis likewise existed. High MET amplification GCN was associated with better MET TKI efficacy.…”

Section: Discussionsupporting

confidence: 61%

“…Studies have shown that high MET amplification is associated with strong oncogenic driving character 24 . A subgroup analysis of the PROFILE 1001 study showed that the ORR in the high MET amplification group (MET/CEP7 ≥ 4.0) was 38.1% with a median PFS of 6.7 months, which was significantly higher than that of the medium or low MET amplification group 25 . In our study, the correlation between MET amplification GCN and prognosis likewise existed.…”

Section: Discussionsupporting

confidence: 60%

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Savolitinib versus crizotinib for treating MET positive non‐small cell lung cancer

et al. 2023

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Background The c‐MET protein, encoded by the mesenchymal‐epithelial transition factor (MET) gene, can regulate cell proliferation, migration and invasion. Studies have shown that it is one of the essential driver genes for non‐small cell lung cancer (NSCLC). Currently, several clinical studies have carried out objective assessments on the efficacy and safety of different types of MET tyrosine kinase inhibitors (TKIs). However, direct cross‐sectional comparisons between different agents are still not available. Methods Our study was a single‐center retrospective clinical study, which collected the data from MET positive NSCLC patients treated with MET TKIs at the Lung Cancer Center of Peking Union Medical College Hospital. We explored the efficacy and safety of crizotinib versus savolitinib in patients with METex14 skipping and MET amplification, separately. Results Patients with METex14 skipping (median PFS = 10.7 months) had a better clinical response to MET TKIs than MET amplification patients (median PFS = 4.1 months). In the METex14 skipping subgroup, savolitinib did not show better survival benefit with significance than crizotinib (p > 0.05). In the MET amplification subgroup, savolitinib (median PFS = 7.1 months) demonstrated a better progression‐free survival benefit than crizotinib (median PFS = 1.4 months), p = 0.05. The most common adverse effects of both MET TKIs were peripheral edema (41.2%), gastrointestinal reactions (23.5%), and liver injury (14.7%). The incidence rate of peripheral edema was higher in savolitinib than crizotinib. Conclusion In METex14 skipping NSCLC patients, the efficacy of savolitinib and crizotinib did not show significant difference. In MET amplification patients, savolitinib showed better efficacy than crizotinib.

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Section: Discussionsupporting

confidence: 61%

Section: Discussionsupporting

confidence: 60%

Savolitinib versus crizotinib for treating MET positive non‐small cell lung cancer

et al. 2023

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“…The ORR in patients with high and intermediate numbers of MET gene copies (50.0% for both) was significantly higher than those without increased MET gene copy number (17.6%), yet survival outcomes for both PFS and OS did not improve. This study showed that an increase in the MET gene copy number was not associated with greater efficacy of nivolumab in patients with NSCLC [22].…”

Section: Discussionmentioning

confidence: 59%

Optimizing treatment strategies for a MET exon 14 skipping mutation in non-small-cell lung cancer: a case report of sequential immunotherapy and targeted therapy and literature review

Grodkiewicz,

Kozieł,

Chmielewska

et al. 2023

Oncol Clin Pract

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The MET exon 14 skipping mutation is found in approximately 3-4% of non-small cell lung cancers (NSCLC). In 2020, the American Food and Drug Administration approved the first drug targeting this mutation. Capmatinib is a selective MET tyrosine kinase inhibitor. In the European Union, capmatinib is used when the patient needs further treatment after receiving immunotherapy or platinum-based chemotherapy, or both. In the described case, due to disease progression during treatment with pembrolizumab and then with platinum-based chemotherapy, next-generation sequencing was performed, which allowed for detection of the MET gene exon 14 skipping mutation. Targeted therapy with capmatinib was the only method of treatment resulting in a partial response to the disease and improvement of the patient's quality of life. This case indicates the importance of detailed molecular diagnosis and selection of the optimal method of treatment to prolong survival of the patient with advanced NSCLC. Due to promising results of research conducted so far, in the future, selective MET tyrosine kinase inhibitors -capmatinib and tepotinib -may become the new standard of first-line treatment in NSCLC patients with the MET exon 14 skipping mutation.

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“…A total of 29 publications providing information on disease characteristics of MET amp NSCLC were identified ( 23 – 51 ). A summary of results from 16 US- or non-US based studies that evaluated demographic and clinical characteristics of patients with NSCLC with or without MET amp is found in Supplementary Table 4 ( 24 – 27 , 29 , 32 , 33 , 35 – 37 , 44 – 47 , 50 , 51 ).…”

Section: Resultsmentioning

confidence: 99%

Non-small cell lung cancer with MET amplification: review of epidemiology, associated disease characteristics, testing procedures, burden, and treatments

Yang,

Mandal,

Liu

et al. 2024

Front. Oncol.

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IntroductionMesenchymal-epidermal transition factor gene amplification (METamp) is being investigated as a therapeutic target in advanced non-small cell lung cancer (NSCLC). We reviewed the epidemiology and disease characteristics associated with primary and secondary METamp, as well as the testing procedures used to identify METamp, in advanced NSCLC. Economic and humanistic burdens, and the practice patterns and treatments under investigation for METamp were also examined.MethodsEmbase and Medline (via ProQuest), ClinicalTrials.gov, and Cochrane Controlled Register of Trials (2015–2022) were systematically searched. Conference abstracts were searched via Embase and conference proceedings websites (2020–2022). The review focused on evidence from the United States; global evidence was included for identified evidence gaps.ResultsThe median rate of primary METamp in NSCLC across the references was 4.8% (n=4 studies) and of secondary METamp (epidermal growth factor receptor [EGFR]-mutant NSCLC) was 15% (n=10). Next-generation sequencing (NGS; n=12) and/or fluorescence in situ hybridization (FISH; n=11) were most frequently used in real-world studies and FISH testing most frequently used in clinical trials (n=9/10). METamp definitions varied among clinical trials using ISH/FISH testing (MET to chromosome 7 centromere ratio of ≥1.8 to ≥3.0; or gene copy number [GCN] ≥5 to ≥10) and among trials using NGS (tissue testing: GCN ≥6; liquid biopsy: MET copy number ≥2.1 to >5). Limited to no data were identified on the economic and humanistic burdens, and real-world treatment of METamp NSCLC. Promising preliminary results from trials enrolling patients with EGFR-mutated, METamp advanced NSCLC progressing on an EGFR-tyrosine kinase inhibitor (TKI) were observed with MET-TKIs (i.e., tepotinib, savolitinib, and capmatinib) in combination with EGFR-TKIs (i.e., gefitinib and osimertinib). For metastatic NSCLC and high-level METamp, monotherapy with capmatinib, crizotinib, and tepotinib are recommended in the 2022 published NSCLC NCCN Guidelines.ConclusionPrimary METamp occurs in approximately 5% of NSCLC cases, and secondary METamp in approximately 15% of cases previously treated with an EGFR inhibitor. Variability in testing methods (including ISH/FISH and NGS) and definitions were observed. Several treatments are promising in treating METamp NSCLC. Additional studies evaluating the clinical, economic, and humanistic burdens are needed.

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MET Amplification and Efficacy of Nivolumab in Patients With NSCLC

Cited by 6 publications

References 51 publications

Savolitinib versus crizotinib for treating MET positive non‐small cell lung cancer

Savolitinib versus crizotinib for treating MET positive non‐small cell lung cancer

Optimizing treatment strategies for a MET exon 14 skipping mutation in non-small-cell lung cancer: a case report of sequential immunotherapy and targeted therapy and literature review

Non-small cell lung cancer with MET amplification: review of epidemiology, associated disease characteristics, testing procedures, burden, and treatments

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